A Study of Luspatercept (ACE-536) to Treat Anemia Due to Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes

Exclusion Criteria

• •The presence of any of the following will exclude a subject from enrollment:
• •1. Prior therapy with disease modifying agents for underlying MDS disease.
• •2. Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
• •3. MDS associated with del 5q cytogenetic abnormality
• •4. Secondary MDS, ie, MDS that is known to have arisen as the result of chemical injury or treatment with chemotherapy and/or radiation for other diseases.
• •5. Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
• •\- iron deficiency to be determined by serum ferritin less than or equal to 15 ug/L and additional testing if clinically indicated (eg, calculated transferrin saturation \[iron/total iron binding capacity less than or equal to 20%\] or bone marrow aspirate stain for iron).
• •6. Prior allogeneic or autologous stem cell transplant
• •7. Known history of diagnosis of acute myeloid leukemia (AML)
• •8. Use of any of the following within 5 weeks prior to randomization:
• •* anticancer cytotoxic chemotherapeutic agent or treatment
• •* corticosteroid, except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS
• •* iron-chelating agents, except for subjects on a stable or decreasing dose for at least 8 weeks prior to randomization
• •* other RBC hematopoietic growth factors (eg, Interleukin-3)
• •* investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to randomization or within 5 weeks, whichever is longer is excluded.
• •9. Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 5 years. However, subjects with the following history/concurrent conditions are allowed:
• •* Basal or squamous cell carcinoma of the skin
• •* Carcinoma in situ of the cervix
• •* Carcinoma in situ of the breast
• •* Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis \[TNM\] clinical staging system)
• •10. Major surgery within 8 weeks prior to randomization. Subjects must have completely recovered from any previous surgery prior to randomization